ZFIN ID: ZDB-PUB-170810-6
Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts
Tokunaga, Y., Shirouzu, M., Sugahara, R., Yoshiura, Y., Kiryu, I., Ototake, M., Nagasawa, T., Somamoto, T., Nakao, M.
Date: 2017
Source: Scientific Reports   7: 7536 (Journal)
Registered Authors:
Keywords: Innate immunity, Innate lymphoid cells, VDJ recombination
MeSH Terms:
  • Adaptive Immunity/genetics
  • Adaptive Immunity/immunology*
  • Animals
  • B-Lymphocytes/immunology*
  • B-Lymphocytes/metabolism
  • Disease Resistance/genetics
  • Disease Resistance/immunology
  • Fish Diseases/genetics
  • Fish Diseases/immunology
  • Fish Diseases/virology
  • Hepatopancreas/immunology
  • Hepatopancreas/metabolism
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/immunology*
  • Homeodomain Proteins/metabolism
  • Homeostasis/genetics
  • Homeostasis/immunology
  • Humans
  • Immunity, Innate/genetics
  • Immunity, Innate/immunology*
  • Mice
  • Spleen/immunology
  • Spleen/metabolism
  • T-Lymphocytes/immunology*
  • T-Lymphocytes/metabolism
  • Zebrafish/genetics
  • Zebrafish/immunology*
  • Zebrafish/metabolism
PubMed: 28790360 Full text @ Sci. Rep.
rag1 -/- zebrafish have been employed in immunological research as a useful immunodeficient vertebrate model, but with only fragmentary evidence for the lack of functional adaptive immunity. rag1-null zebrafish exhibit differences from their human and murine counterparts in that they can be maintained without any specific pathogen-free conditions. To define the immunodeficient status of rag1 -/- zebrafish, we obtained further functional evidence on T- and B-cell deficiency in the fish at the protein, cellular, and organism levels. Our developed microscale assays provided evidence that rag1 -/- fish do not possess serum IgM protein, that they do not achieve specific protection even after vaccination, and that they cannot induce antigen-specific CTL activity. The mortality rate in non-vaccinated fish suggests that rag1 -/- fish possess innate protection equivalent to that of rag1 +/- fish. Furthermore, poly(I:C)-induced immune responses revealed that the organ that controls anti-viral immunity is shifted from the spleen to the hepatopancreas due to the absence of T- and B-cell function, implying that immune homeostasis may change to an underside mode in rag-null fish. These findings suggest that the teleost relies heavily on innate immunity. Thus, this model could better highlight innate immunity in animals that lack adaptive immunity than mouse models.